1. Field of the Invention:
The present invention relates to polylactic acid microspheres containing a physiologically active substance and a process for producing the same. 2. Description of the Prior Art:
The development of new pharmaceutical preparations based on the drug delivery system is being studied actively through the medical engineering approach and biopharmaceutic approach. The results of the development include new dosage forms prepared by utilizing polymeric thin membrane, deformed solid surface, liposome, emulsion, etc. Among them the one based on biodegradable polylactic acid is attracting attention.
Polylactic acid can be used as the polymer matrix for microspheres or as the coating substance for microcapsules. Microspheres are produced by the so-called solvent-evaporation drying process. According to this process, the polymer and drug are dissolved in a common solvent, a phase-separating the agent is added to the solution for emulsification, the solvent is distilled away, and residual fine particles are collected. (Refer to Chem. Pharm. Bull. 30, 2621-2628 (1982) and Japanese Patent Laid-open No. 33414/1980.) On the other hand, microcapsules are produced by the so-called phase-separation process which involves the steps of dispersing a physiologically active substance in a polylactic acid solution in which the substance is insoluble, adding a non-solvent for the polymer to bring about coacervation, and curing the polymer by a proper means. (Refer to Japanese Patent Laid-open No. 48923/1985.) According to the other known process, microencapsulation is accomplished by the in-water drying of three-layer emulsion.
The above-mentioned prior arts provide a drug delivery system which produces a certain effect but suffer from the limitations that they are not able to prepare microspheres having a diameter as small as several microns and they involve complicated processes. With this in mind, the present inventors studied the process for producing fine microspheres for sustained release preparation in a simple manner by the solvent-evaporation drying process. As a result, it was found that it is possible to produce microspheres having a diameter of several microns if the solution is treated with ultrasonic wave during emulsification. This finding led to the present invention.